Saturday, January 17, 2015

Chronic pain affects an estimated 100 million Americans, and between 5 to 8 million use opioids for long-term pain management. Data shows the number of prescriptions written for opioids as well opioid overdose deaths have skyrocketed in recent years, highlighting a growing addiction problem in the U.S. In response, the National Institutes of Health (NIH) released a report on Monday citing major gaps in the way American clinicians are treating pain.

In September, the NIH held a workshop to review chronic pain treatment with a panel of seven experts and more than 20 speakers. The NIH also reviewed relevant research on how pain should be treated.

An independent panel convened by the National Institutes of Health concluded that individualized, patient-centered care is needed to treat and monitor the estimated 100 million Americans living with chronic pain. To achieve this aim, the panel recommends more research and development around the evidence-based, multidisciplinary approaches needed to balance patient perspectives, desired outcomes, and safety.

"Persons living with chronic pain have often been grouped into a single category, and treatment approaches have been generalized with little evidence to support this practice," said Dr. David B. Reuben, panel chair and professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. "Chronic pain spans a multitude of conditions, presents in different ways, and requires an individualized, multifaceted approach."

Chronic pain is often treated with prescription opioids, but the panel noted widespread concern with this practice. Although some patients benefit from such treatment, there are no long-term studies on the effectiveness of opioids related to pain, function, or quality of life. There is not enough research on the long-term safety of opioid use. However, there are well-documented potential adverse outcomes, including substantial side effects (e.g., nausea, mental clouding, respiratory depression), physical dependence, and overdose—with approximately 17,000 opioid-related overdose deaths reported in 2011.

"Clearly, there are patients for whom opioids are the best treatment for their chronic pain. However, for others, there are likely to be more effective approaches," stated Dr. Reuben. "The challenge is to identify the conditions for which opioid use is most appropriate, the alternatives for those who are unlikely to benefit from opioids, and the best approach to ensuring that every patient's individual needs are met by a patient-centered health care system."

The panel identified several barriers to implementing evidence-based, patient-centered care. For example, many clinicians do not have tools to assess patient measures of pain, quality of life, and adverse outcomes. Primary care practices often do not have access to multidisciplinary experts, such as pain management specialists. Insurance plans may not cover team-based, integrative approaches that promote comprehensive, holistic care. In addition, some plans do not offer effective non-opioid drugs as first-line treatment for chronic pain, thus limiting a clinician's ability to explore other avenues of treatment. Once a health provider has made the decision to use opioids, there are insufficient data on drug characteristics, dosing strategies, or tapering to effectively guide clinical care.

"Chronic pain spans a multitude of conditions, presents in different ways, and requires an individualized, multifaceted approach."

—Dr. David B. ReubenPanel chair and professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles

"We have inadequate knowledge about treating various types of pain and how to balance effectiveness with potential harms. We also have a dysfunctional health care delivery system that promotes the easiest rather than the best approach to addressing pain," noted Dr. Reuben.

To address knowledge gaps, the panel cited a need for more research on pain, multidisciplinary pain interventions, the long-term effectiveness and safety of opioids, as well as optimal opioid management and risk mitigation strategies. However, because well-designed longitudinal studies can be large, expensive, and difficult for recruitment, the panel encouraged the development of new research design and analytic methods to answer important research and clinical questions.

The panel also recommended engaging electronic health record vendors and health systems to provide pain management decision support tools for clinicians. In addition, the panel advised the NIH and other federal agencies to sponsor more conferences to harmonize pain assessment and treatment guidelines to facilitate consistent clinical care for the treatment of chronic pain.

The panel will hold a press telebriefing on Friday, Jan. 16, at 3 p.m. EST to discuss its findings with members of the media. To participate, call 888-428-7458 (toll free for United States and Canada) or 862-255-5398 (toll for other international callers) and reference the NIH Pathways to Prevention program on The Role of Opioids in the Treatment of Chronic Pain. Audio playback will be available shortly after the conclusion of the telebriefing and can be accessed by calling 888-640-7743 (United States and Canada) or 754-333-7735 (other international callers) and entering replay code 114001.

To better understand the role of opioids in the treatment of chronic pain, the NIH Office of Disease Prevention (ODP) convened a Pathways to Prevention workshop on Sept. 29–30, 2014, to assess the available scientific evidence. The panel's final report, which identifies future research and clinical priorities, incorporates the panel's assessment of an evidence report, expert presentations, audience input, and public comments. The panel's report, which is an independent report and not a policy statement of the NIH or the federal government, is now available at https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/opioids-chronic-pain/workshop-resources.

Friday, January 16, 2015

It's happening, says the woman I love to someone in the other room. The someone is most likely her sister, and I hear the shuffle of clogs on the ruined carpet, the swish and swirl of her turquoise dress. I feel the shadow of her body in the doorway. I hear her breathing, tiny bursts of air through the nose and mouth. I feel and hear everything, but I am not a body. And because I am no longer a body, I do not register sound or voice. I do not register anything. Even my presence on the scratchy carpet. I do not know that I have been lying in the lap of the woman I love as she soothes my sweat-drenched hair, as she whispers that this will pass. I do not hear her because I do not have ears. I do not have eyes. I do not see the hazy outline of her humid-frizzed hair or the worry etched in her face or how she looks down at me and then out the window, out past the dilapidated houses of this rundown block in Lafayette, Colorado, past the Rockies rising in jagged edges to snowy peaks, past logical explanation. Because right now, I do not register logic. Because this pain is not logical. This pain makes me whimper, makes me produce a noise that is octaves higher and sharper than I can otherwise make. I become a supplicant to its needs. I have a mouth. Of this I am sure. I have a mouth but it acts without my guidance. Saliva seeps from corners. Lips chapped as cracked earth. The woman I love feeds me water. I sip from a straw, but all of it dribbles out from the corners of my mouth. All of it wetting my cheeks and chin, like a child sloppy with food. I am a child. I am helpless. I am without strength. I am without will. I believe I might die. That this might be the end of me, this moment. I believe that death would be a relief from it all.

Hang on, she says. It's almost over, she says. The end is in sight, she says.

"Glial activation is accompanied by many cellular responses, which include the production and release of substances (such as so-called 'pro-inflammatory cytokines') that can sensitize the pain pathways in the central nervous system," he explained. "Thus, glial activation is not a mere reaction to a pain state but actively contributes to the establishment and/or maintenance of persistent pain."

To test their hypothesis that patients with chronic pain demonstrate in vivo activation of brain glia, Dr. Loggia's team imaged the brains of 19 individuals diagnosed with chronic low back pain as well as 25 pain-free healthy volunteers using 11C-PBR28, a PET radioligand that binds to the translocator protein (TSPO), a protein upregulated in activated microglia and reactive astrocytes in animal models of pain.

In the thalamic region of interest, 11C-PBR28 uptake was significantly higher in patients with chronic low back pain than in healthy controls (p<0.01 left thalamus, p<0.05 right thalamus), according to the January 12 Brain online report.

Each patient exhibited higher 11C-PBR28 uptakes than his/her age-, sex-, and TSPO genotype-matched control in the thalamus, and there were no brain regions for which the healthy controls showed statistically higher uptakes than the patients with chronic low back pain.

11C-PBR28 uptakes, and presumably TSPO levels, were negatively associated with pain measures and with circulating levels of proinflammatory cytokines in the chronic pain patients.

"It's important to stress that although TSPO upregulation is a marker of glial activation and therefore of a pro-inflammatory state, animal studies suggest that its role is actually to limit the magnitude of glial responses after their initiation, thereby promoting the return to pre-injury pain-free status and recovery from pain," Dr. Loggia explained. "This means that what we are imaging may be the process of glial cells trying to 'calm down' after being activated by the pain. Thus, subjects with low levels of pain-related TSPO upregulation on activated glia may be less able to adequately inhibit neuroinflammatory responses, and have a more exaggerated response that ultimately leads to more inflammation and pain."

You're not imagining the pain. But your brain might be behind it, nonetheless. For the first time, it is possible to distinguish between brain activity associated with pain from a physical cause, such as an injury, and that associated with pain linked to your state of mind.

A fifth of the world's population is thought to experience some kind of chronic pain – that which has lasted longer than three months. If the pain has no clear cause, people can find themselves fobbed off by doctors who they feel don't believe them, or given ineffective or addictive painkillers.

But a study led by Tor Wager at the University of Colorado, Boulder, now reveals that there are two patterns of brain activity related to pain. One day, brain scans could be used to work out your relative components of each, helping to guide treatment.

"Pain has always been a bit of a puzzle," says Ben Seymour, a neuroscientist at the University of Cambridge. Hearing or vision, for example, can be traced from sensory organs to distinct brain regions, but pain is more complex, and incorporates thoughts and emotions. For example, studies have linked depression and anxiety to the development of pain conditions, and volunteers put in bad moods have a lower tolerance for pain.

So does this mean we can think our way into or out of pain? To find out, Wager and his colleagues used fMRI to look at the brain activity of 33 healthy adults while they were feeling pain. First, the team watched the changing activity as they applied increasing heat to the volunteers' arms. As the heat became painful, a range of brain structures lit up. The pattern was common to all the volunteers, so Wager's team called it the neurologic pain signature.

The group then examined whether the volunteers could control the pain by thought alone. "We asked them to rethink their pain, either as a blistering heat, or as a warm blanket on a cool day," Wager says. Although the volunteers couldn't change the level of activity in the neurologic pain signature, they could alter the amount of pain they felt. As they did this, a distinct set of brain structures linking the nucleus accumbens and ventromedial prefrontal cortex became active (PLoS Biology, doi.org/x55).

"It's a major finding," says Vania Apkarian at Northwestern University in Chicago. "For the first time, we've established the possibility of modulating pain through two different pathways."

Wednesday, January 14, 2015

Doctors aren't entirely sure what triggers rheumatoid arthritis, a disease in which the body turns on itself to attack the joints, but an emerging body of research is focusing on a potential culprit: the bacteria that live in our intestines.

Several recent studies have found intriguing links between gut microbes, rheumatoid arthritis, and other diseases in which the body's immune system goes awry and attacks its own tissue.

A study published in 2013 by Jose Scher, a rheumatologist at New York University, found that people with rheumatoid arthritis were much more likely to have a bug called Prevotella copri in their intestines than people that did not have the disease. In another study published in October, Scher found that patients with psoriatic arthritis, another kind of autoimmune joint disease, had significantly lower levels of other types of intestinal bacteria.

Saturday, January 03, 2015

Complex regional pain syndrome (CRPS) is a chronic, predominantly neuropathic and partly musculoskeletal pain disorder often associated with autonomic disturbances. It is divided into 2 types, reflecting the absence or presence of a nerve injury.

Patients with either type may exhibit symptoms such as burning pain, hyperalgesia, and/or allodynia with an element of musculoskeletal pain. CRPS can be distinguished from other types of neuropathic pain by the presence of regional spread as opposed to a pattern more consistent with neuralgia or peripheral neuropathy. Autonomic dysfunction (such as altered sweating, changes in skin color, or changes in skin temperature); trophic changes to the skin, hair, and nails; and altered motor function (such as weakness, muscle atrophy, decreased range of motion, paralysis, tremor, or spasticity) also can be present.

At least 50,000 new cases of CRPS are diagnosed in the United States annually.1 Although the incidence rate is subject to debate, a large epidemiologic study from The Netherlands involving 600,000 patients suggests an incidence of 26.2 per 100,000 individuals. The study also found that women are 3 times more likely to be affected, with postmenopausal women having the greatest risk.